O13: TUMOUR STROMAL CELLS - A CULPRIT IN BREAST CANCER RECURRENCE AFTER NEOADJUVANT CHEMOTHERAPY

The goal of neoadjuvant chemothepaeutics(NACs) and surgical excision of breast cancer is to control and ultimately eliminate the malignant tumour. Despite advances in treatment, a subset of patients will develop disease recurrence. Tumour stromal cells(TSCs) are non-cancerous cells that support malignancy within the tumour microenvironment(TME). In particular, TSCs can suppress the host immune response to tumour. It is unclear if NACs affect the survival of–or alter the immunosuppressive functions of TSCs in breast cancer patients and if this correlates with recurrance or chemoresistance? Method TSCs and Tumour Associated Normal Stromal Cells(TANs) were isolated from tissue harvested from breast cancer patients at surgery. Clonogenic survival assays were performed following exposure to increasing doses of Paclitaxel (range 0-1000nM), Cyclophosphamide (range 0-3μM) and Doxorubicin (0-100nM). TSCs were co-cultured with CD4+ and CD8+ T-cells to determine the effect of chemotherapeutics on their ability to suppress T-cell proliferation. Result TSCs(n=5) are less susceptible to the cytotoxic effects of chemotherapy compared to TANs with 21%(p-0.0001), 21%(p-0.001) and 15%(p-0.026) more colonies across all doses of Paclitaxel, Cyclophosphamide and Doxorubicin respectively. Chemo naïve TSCs suppressed CD4+ and CD8+ T-Cell proliferation by 44% and 20.5% respectively(p-0.001, p-0.042). Interestingly, Paclitaxel-treated TSCs suppressed CD4+ proliferation by a further 11.1%(p-0.047) and CD8+ proliferation by 35.6%(p-0.017). Additionally, Cyclophosphamide-treated TSCs enhanced CD8+ suppression by 25.6%(p-0.029). Conclusion Our data indicate that NACs enhance the immunosuppressive function of TSCs - potentially creating an immune inert TME in vivo. Future studies will explore the correlation between NAC treatment, immunosuppressive activities within patient tumours/blood and recurrence. Take-home message After neoadjuvant chemotherapy, Tumour stromal cells are highly immunosuppressive and may contribute to breast cancer recurrence.